Oral microbiota promoting method

ABSTRACT

A method of promoting a desired oral microbiota in a subject to treat an allergy related respiratory condition, the method including providing an edible composition including an amino acid containing ingredient comprising L-arginine wherein the composition is provided contained and at least partially dissolved within an oral cavity of the subject for a period of at least from about 10 seconds to about an hour on a daily basis of at least two consecutive days.

The disclosure generally relates to oral cavity microbiota promotingcompositions including sweetened prebiotic foods and methods for makingand using the same. More particularly, the disclosure relates tocompositions and methods for making and using the same that may have theadvantageous effect of modulating the oral microbiota which may therebypromote the naturally occurring health of the immune system includingreducing respiratory allergic reactions.

BACKGROUND

In general, the prevalence of allergic diseases has dramaticallyincreased in recent decades and currently affects more than sixtymillion people in the United States, reducing the quality of life. It isbelieved and has been found that the presence of certain oral bacteriaspecies/strains may affect the aggressiveness of response of the immunesystem, for example with respect to allergies. More specifically, whilenot intending to be bound by any health claims, it is believed that thereduction of normally occurring oral bacteria in the normally occurringoral microbiota, for example, by aggressive dental hygiene practices,may serve to make non-pathogenic antigens, such as pollen, moreprevalent and visible to the immune system. It is further believed, thatas a result, non-pathogenic antigens, such as those related to allergensmay be more readily targeted by the immune system, leading toexacerbated allergic reactions.

For example, oral hygiene hypothesis (OHH) is one aspect of a moregeneral hygiene hypothesis (HH), which was proposed more than twodecades ago (see Strachan, D. P. “Hay fever, hygiene, and householdsize”, British Medical Journal 299, 1259-1260 (1989)) to explain therise in allergic diseases. Numerous scientific studies have sinceprovided support for HH, generally showing a relation between increasedexhibition of allergies in association with modern social practices,such as formula infant feeding, antibiotic use, urban living, andreduction in family size (see e.g., Okada, H., Kuhn, C., Feillet, H. &Bach, J. F., “The hygiene hypothesis for autoimmune and allergicdiseases: an update” Clin. Exp. Immunol. 160, 1-9 (2010)). Although themolecular mechanisms of immune system modulation by gut microbiota arewell understood, efforts to reduce allergic reactions through microbialintervention, such as by the use of probiotics have shown inconsistentresults.

Extensive oral hygiene practices, according to oral hygiene hypothesis(Han, C S., “A specific hygiene hypothesis” Med. Hypotheses 2016 August;93:146-149), are believed to cause the exacerbation of naturallyoccurring respiratory allergies, such as allergic rhinitis (AR), one ofthe most common allergic conditions.

There is therefore a need for a composition including an oral cavitymicrobiota promoting substance and method of using the same that has theeffect of promoting a healthy oral microbiota that promotes the healthyoperation of the immune system which may have the functional effect ofpromoting an improved response to allergens.

It is an object of the invention to provide a composition including anoral cavity microbiota promoting substance and method of using the samethat has the effect of promoting a healthy oral microbiota that promotesthe healthy operation of the immune system which may have the functionaleffect of promoting an improved response to allergens.

SUMMARY

A method of promoting a desired oral microbiota in a subject to treat anallergy related respiratory condition, the method including providing anedible composition including an amino acid containing ingredientcomprising L-arginine wherein the composition is provided contained andat least partially dissolved within an oral cavity of the subject for aperiod of at least from about 10 seconds to about 1 hour on a dailybasis of at least two consecutive days.

DETAILED DESCRIPTION

The following detailed description is merely exemplary in nature and isnot intended to limit the described embodiments or the application anduses of the described embodiments. As used herein, the word “exemplary”or “illustrative” means “serving as an example, instance, orillustration.” Any implementation described herein as “exemplary” or“illustrative” is not necessarily to be construed as preferred oradvantageous over other implementations. All of the implementationsdescribed below are exemplary implementations provided to enable personsskilled in the art to practice the disclosure and are not intended tolimit the scope of the appended claims. Furthermore, there is nointention to be bound by any expressed or implied theory presented inthe preceding technical field, background, brief summary or thefollowing detailed description.

It is believed, and has been found that according to the oral hygienehypothesis (OHH) noted above, that persistent and intensive hygienepractices, together with other life events, such as fever and/orantibiotic usage, will likely change the oral microbiota of anindividual. The oral cavity is a complex environment with many differentbiological niches, such as the tongue, gum, and teeth. Normallyoccurring microbiota associated with these niches are different and arebelieved to have a different effect on normal functioning of the immunesystem.

Likewise, it is believed, and has been unexpectedly found, that theintroduction of selected microbiota-promoting substances into the oralcavity in a controlled manner, may promote desired naturally occurringoral bacteria species/strains, which may in turn have an associatedeffect of modulating or reducing the intensity of certain types ofallergic reactions, including those associated with allergic rhinitis(AR) one of the most common allergic reactions including symptoms suchas any combination of a runny or stuffy nose, sneezing, itchy/red eyes,coughing, and congestion.

While not intending to be bound by any particular theory of operation,and making no specific health claims, it is believed that oralmicrobiota interact with the host largely through metabolites producedby its relevant bacterial members. Those metabolites, such as but notlimited to short chain fatty acid, may influence the function ofmultiple biologic systems and organs, such as the immune system. Missingor severe reduction of the relevant bacteria may cause malfunctioning ofthe immune system, such as causing over sensitivity to allergens.

Therefore, it is believed that the immune system response to theallergen may be modulated such that the associated allergic reactionsymptoms are suppressed relative to what an allergic reaction may bewith an unhealthy level of or different microbiota. It is furtherbelieved and evidence suggests that over time, as a result of promotinga healthy oral microbiota with selected microbiota-promoting substancesthat the immune system may function in a healthy manner with a healthyresponse to allergens.

Furthermore, due to the connectivity among mouth and respiratory ductand lungs, a healthy oral microbiota may lead to a healthy microbiota inthe lungs as well. Eventually the method may benefit the healthyfunctioning of the immune system which may in turn have a healthyresponse not only to allergic rhinitis but also the relevant diseases inthe lungs, such as asthma.

In one embodiment, an oral microbiota promoting composition may beprovided into an oral cavity that may have the effect of promotingdesired microbiota within an oral cavity.

In another embodiment, a method of applying an oral microbiota promotingcomposition (prebiotic) may be provided that may have the effect ofpromoting desired microbiota within an oral cavity and have the desiredfunctional effect of treating a respiratory condition including allergicrhinitis.

In one embodiment, a method of applying an oral microbiota promotingcomposition may include multiple instances of introduction of thecomposition into the oral cavity (mouth) in the form or a solid, powder,paste, or liquid in the amount of about 1 gm to about 500 gms at onetime or multiple times in fractional amounts. Where the oral microbiotapromoting composition is in the form of liquid, the method may includedissolving the composition in a liquid

In another embodiment, a method of applying an oral microbiota promotingcomposition may include swallowing the composition followingintroduction of the composition into the oral cavity and following aperiod of retaining the composition within the mouth for a select periodof time including e.g., chewing, gargling, and/or sublimating(dissolving) the composition while within the oral cavity.

In another embodiment, a method of applying an oral microbiota promotingcomposition may include removing the composition following introductioninto the oral cavity by expelling (e.g., pulling out or spitting-out)the microbiota promoting composition following a period of retaining thecomposition within the mouth.

In another embodiment, a method of applying an oral microbiota promotingcomposition may include retaining the microbiota promoting compositionwithin the oral cavity from about 10 seconds to about an hour, morepreferably, from about 5 minutes to about 30 minutes on a daily basisfor a period of about 2 days to about 60 days.

In another embodiment, a method of applying an oral microbiota promotingcomposition may include introducing the microbiota promoting compositionfor relatively short periods several times a day, for example from about1 second to about 30 seconds, each from about 3 to about 10 times a dayfor a period of about 2 days to about 60 days.

In another embodiment, a method of applying an oral microbiota promotingcomposition may include extending the periods of introduction of themicrobiota promoting composition into the oral cavity, for example, fromabout every 3 days to about every 10 days, including stopping theintroduction of the composition following the disappearance of allergysymptoms.

In another embodiment, a method of applying an oral microbiota promotingcomposition may include at least partially removing a mucosal film(biofilm) from within the oral cavity prior to or while administeringthe microbiota promoting composition to the oral cavity.

It will be appreciated that the biofilm may be at least partiallyremoved by raising the whole body temperature for a short time, forexample, with conventional biological or physical means.

In a related embodiment, the biofilm may be at least partially removedby rinsing out (optionally including scrubbing or rubbing) the oralcavity (mouth) with a heated water containing liquid, such as water, ata temperature of from about to about 130 degrees Fahrenheit prior toapplying the oral microbiota promoting composition to the oral cavity.It will be appreciated that rinsing with a hot water containing fluid asnoted may advantageously at least partially remove a biofilm fromsurfaces within the oral cavity, thereby improving the operation of theoral microbiota promoting composition. The oral rinsing may includeperiodic rinsing, for example, each for about 10 seconds to about 30seconds over a period of from about 5 to about 15 minutes.

In another embodiment, a method of applying an oral microbiota promotingcomposition may include at least one of brushing and rubbing portions ofthe oral cavity with the hot water containing fluid at a temperature offrom about 100 to about 130 degrees Fahrenheit including at least thetongue, for example, with at least one of a brush, such as a toothbrush,and/or a wet cloth.

In another embodiment, the oral microbiota promoting composition may beformulated into oral dosage forms such as tablets, caplets, andcapsules, or a powder formulation or that may be dissolved in a liquid,for example diluted in a liquid having a ratio of from about 1:1 toabout 1:500 with respect to either weight or volume of the liquid (e.g.,the liquid being larger number).

In another embodiment, the oral microbiota promoting composition may beformulated or manufactured as a chewing gum or candy, or other ediblecarrier, for example as an additive having a ratio of from about 1:1 toabout 1:500 with respect to either weight or volume of the ediblecarrier (e.g., larger number).

In another embodiment, the oral microbiota promoting composition may beformulated as an additive to an oral hygiene product acting as acarrier, such as toothpaste or mouthwash, the microbiota promotingcomposition having a ratio of from about 1:1 to about 1:500 with respectto either weight or volume of the oral hygiene product.

In another embodiment, in a method of manufacturing an oral microbiotapromoting composition may be formulated having an edible foodstuff as acarrier, the microbiota promoting composition having a ratio of fromabout 1:1 to about 1:500 with respect to either weight or volume of theedible foodstuff.

In one embodiment, the desired microbial species/strains promoted in theoral cavity by the oral microbiota promoting composition may benaturally occurring within the oral cavity and/or may be providedseparately or within the oral microbiota promoting composition.

In a related embodiment, the desired microbial species/strains arepresent in the oral cavity or in the oral microbiota promotingcomposition at a level of from about 1000 to about 1,000,000,000 livingcells.

It will be appreciated that the desired microbial species/strains arenaturally occurring and/or may be obtained commercially and handled inaccordance with any applicable safety requirements.

In another embodiment, the desired microbial species/strains promoted inthe oral cavity by the oral microbiota promoting composition may includeat least a first microbial species that can attach to surfaces (e.g.,teeth, tongue, mouth) within the oral cavity and at least one secondmicrobial species that may attach to the same or different surfacesand/or may attach to the at least first microbial species.

In a related embodiment, the at least a first and second microbialspecies may produce a product, such as a sugar containing moiety, thatmay be metabolized by the other of the at least a first and secondmicrobial species.

In one embodiment, one of the desired microbial members promoted withinthe oral cavity promoted by the oral microbiota promoting compositionmay include one or more live bacterium with lactate fermentingcapability such as, but not limited to Veillonella, which further mayinclude one or more of associated species, such as, but not limited to,V. Dispar and V. Parvula.

In one embodiment, one of the desired microbial species/strains promotedwithin the oral cavity promoted by the oral microbiota promotingcomposition may include one or more live lactic acid producing bacteriumsuch as but not limited to Streptococcus including one or more ofassociated species, such as, but not limited to, S. salivarius and S.thermophilus.

In a related embodiment, the desired microbial species/strains promotedwithin the oral cavity by the oral microbiota promoting composition mayinclude at least one live lactic acid producing bacterium and at leastone live lactate fermenting bacterium such as, but not limited to,respectively, Veillonella and Streptococcus and their respectivelyassociated preferred species stated above.

In another embodiment, an oral microbiota promoting composition isprovided that includes at least one amino acid or amino acid containingsubstance including at least L-arginine. The at least one amino acid mayfurther or alternately include at least one of L-cysteine, DL-asparticacid, L-glutamic acid, L-serine and L-tyrosine including phosphates,salts, acids, and enzymes comprising the same.

In a related embodiment, the at least one amino acid, may be present inthe oral microbiota promoting composition at a weight percent level offrom about 0.1 wt. % to about 99.9 wt. %, more preferably, from about 5wt % to about 95 wt %, even more preferably from about 20 wt % to 80 wt%.

In another embodiment, an oral microbiota promoting composition isprovided that includes at least one sugar containing substance and atleast one amino acid containing substance. The at least one sugarcontaining substance may include at least one monosaccharide,disaccharide, oligosaccharide, and polysaccharide.

Exemplary monosaccharides may include but are not limited to aldohexosessuch as but not limited to mannose including associated isomers,phosphates, salts, acids, and enzymes comprising the same.

Exemplary disaccharides may include but are not limited to disaccharidesincluding at least one of galactose and glucose, such as but not limitedto lactose, sucrose, malibiose, maltose, cellobiose and trehalose (alsoknown as mycose or tremalose) including associated isomers, phosphates,salts, acids, and enzymes comprising the same.

Exemplary oligosaccharides may include but are not limited totrisaccharides including at least one or more of galactose, glucose, andfructose, such as but not limited to raffinose (also known as melitose),stachyose, and verbascose, including associated isomers, phosphates,salts, acids, and enzymes comprising the same.

Further, Exemplary polysaccharides may include but are not limited toone or more polysaccharide polymers, such as, but not limited topolysaccharides including malotriose units, including but not limited topullulan, and fructose polymers, such as, but not limited to inulin andfurther including associated isomers, phosphates, salts, acids, andenzymes comprising the same.

In a related embodiment, the at least one disaccharide may be present inthe oral microbiota promoting composition at a weight percent level offrom about 0.1 wt. % to about 99.9 wt. %, more preferably, from about 5wt % to about 95 wt %, even more preferably from about 20 wt % to 80 wt%.

In a related embodiment, the at least one oligosaccharide may be presentin the oral microbiota promoting composition at a weight percent levelof from about 0.1 wt. % to about 99.9 wt. %, more preferably, from about5 wt % to about 95 wt %, even more preferably from about 20 wt % to 80wt %.

In a related embodiment, the at least one polysaccharide may be presentin the oral microbiota promoting composition at a weight percent levelof from about 0.1 wt. % to about 99.9 wt. %, more preferably, from about5 wt % to about 95 wt %, even more preferably from about 20 wt % to 80wt %.

In another embodiment, the oral microbiota promoting composition mayinclude at least one prebiotic fiber. Exemplary prebiotic fibers mayinclude but are not limited to inulin.

In a related embodiment, the at least one prebiotic fiber may be presentin the oral microbiota promoting composition at a weight percent levelof from about 0.1 wt. % to about 99.9 wt. %, more preferably, from about5 wt % to about 95 wt %, even more preferably from about 10 wt % to 30wt %.

In another embodiment the oral microbiota promoting composition mayinclude additives such as one or more of carbohydrates, amino acids,salts, flavorants, proteins, surfactants, emulsifiers, flavonoids,alcohols, synthetic sweeteners, food preserving agents, and combinationsthereof.

In one embodiment, the oral microbiota promoting composition may furtherinclude conventional foodstuffs such as one or more of brown sugar,syrup, honey, chocolate, nuts, almonds, spices, cinnamon, and vanilla.

In a specific exemplary embodiment, an example of making an edibleFoodstuff oral microbiota promoting composition is provided below inExample 1:

Example 1

1 cup raffinose

1 cup trehalose

2 tablespoons mannose

1 cup lactose

½ cup maltose

½ cup L-arginine

2 tablespoons pullulan

1 cup inulin

1 cup dark brown sugar

½ cup corn syrup

½ cup honey

1 cup milk chocolate

1 cup chocolate chips

¼ cup toasted almonds (small chips)

¼ tablespoon cinnamon

¼ tablespoon vanilla extract

In one embodiment, the above ingredients may be admixed and heated to atemperature sufficient to melt or liquefy, preferably avoiding boilingfor an extended period and then poured into a container to cool.

In another embodiment, live bacterium, in accordance with safetyrequirements or limitations, may be added following cooling (e.g., as acoating). It will be appreciated that adding the bacterium may belimited by applicable safety precautions and may reduce the shelf lifeof the product.

Although the embodiments of this disclosure have been described withrespect to certain exemplary embodiments, it is to be understood thatthe specific embodiments are for purposes of illustration and notlimitation, as other variations will occur to those of skill in the art.

What is claimed is:
 1. A method of promoting a desired oral microbiotato treat an allergy related respiratory condition comprising in asubject in need of such treatment: providing a preformulated prebioticedible composition comprising: an amino acid containing ingredientcomprising individual molecules of L-arginine; removing a biofilm fromsurfaces within an oral cavity by heating the inside of the oral cavityto a temperature of about 100 deg F. to about 130 deg F.; whereinfollowing removal of the biofilm, the composition is provided containedand at least partially dissolved within an oral cavity of the subjectfor a period of at least from about 30 seconds to about an hour on adaily basis of at least two consecutive days to promote an increasedconcentration of selected oral microbiota, the selected microbiotacomprising Veillonella and Streptococcus, to thereby treat an allergyrelated respiratory condition.
 2. The method of claim 1, wherein thecomposition is provided in a carrier.
 3. The method of claim 2, whereinthe carrier comprises a solid, powder or liquid.
 4. The method of claim2, wherein the carrier comprises one or more of a chewable tablet, anedible capsule, and a hygienic paste, and an edible food.
 5. The methodof claim 1, wherein the composition is provided within the oral cavityfrom a period of from about 2 consecutive days to about 60 consecutivedays.
 6. The method of claim 1, wherein heating the inside of the oralcavity comprises periodic oral rinsing with a heated liquid, eachrinsing for about 10 seconds to about 1 minute over a period of fromabout 5 to about 15 minutes.
 7. The method of claim 6, wherein removalof the biofilm comprises at least one of brushing and rubbing the oralcavity with the heated liquid.
 8. The method of claim 1, wherein the atleast one amino acid further comprises at least one of L-cysteine,DL-aspartic acid, L-glutamic acid, L-serine, and L-tyrosine.
 9. Themethod of claim 1, wherein the amino acid containing ingredient ispresent in the composition at a weight percent level of from about 0.1wt. % to about 99.9 wt. %.
 10. The method of claim 1, wherein thecomposition further comprises a sugar containing ingredient, the sugarcomprising one or more of monosaccharides, disaccharides,oligosaccharides, and polysaccharides.
 11. The method of claim 10,wherein the sugar comprises one or more of mannose, lactose, malibiose,maltose, cellobiose, trehalose, raffinose.
 12. The method of claim 10,wherein the composition further comprises polysaccharide polymers. 13.The method of claim 12, wherein the polysaccharide polymers comprise oneor more of pullulan and inulin.
 14. The method of claim 10, wherein thesugar is present in the composition at a weight percent level of fromabout 0.5 wt. % to about 95 wt. %.
 15. The method of claim 1, wherein atleast one of the composition and oral cavity further comprises livebacteria comprising a lactic acid producing bacterium and a lactatefermenting bacterium at a level of from about 1000 to about1,000,000,000 living cells.
 16. The method of claim 15, wherein thecomposition comprises the live bacteria at a level of from about 1000 toabout 1,000,000,000 living cells.
 17. The method of claim 1, wherein theamino acid containing ingredient is present in the composition at aweight percent level of from about 5.0 wt. % to about 95.0 wt. %. 18.The method of claim 1, wherein Streptococcus includes one or more of S.salivarius and S. thermophilus.
 19. The method of claim 1, whereinVeillonella comprises one or more of V. Dispar and V. Parvula.
 20. Themethod of claim 10, wherein the sugar is present in the composition at aweight percent level of from about 5.0 wt. % to about 95.0 wt. %.